Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation
Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation
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DOI：
10.1158/0008-5472.can-05-4566
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发表时间：
2006-07-01
期刊：
影响因子：
11.2
通讯作者：
Sanchez, Cristina
中科院分区：
文献类型：
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作者：
Caffarel, Maria M.;Sarrio, David;Sanchez, Cristina
有人提出大麻素参与控制细胞命运。因此，这些化合物可以根据细胞类型及其生理病理背景以不同的方式调节增殖、分化和存活。然而，大麻素对细胞周期的影响知之甚少，细胞周期是控制细胞命运的主要过程。在这里，我们发现Delta(9)-四氢大麻酚（THC）通过激活CB2大麻素受体，通过阻断细胞周期的进展和诱导凋亡来减少人乳腺癌细胞的增殖。特别是，THC通过下调Cdc2来抑制G(2)-M中的细胞，这表明过表达Cdc2的细胞对THC的敏感性降低。有趣的是，正常人乳腺上皮细胞的增殖模式受四氢大麻酚的影响要小得多。我们还通过实时定量PCR分析了CB1和CB2大麻素受体在一系列人乳腺肿瘤和非肿瘤样本中的表达。我们发现CB2的表达与肿瘤的组织学分级之间存在相关性。此外，CB2表达与其他预后和预测价值的标志物（如雌激素受体、孕激素受体和ERBB2/HER-2癌基因）之间也存在关联。重要的是，在非肿瘤乳腺组织中未检测到显著的CB2表达。综上所述，这些数据可能为大麻素治疗乳腺癌奠定基础。
It has been proposed that cannabinoids are involved in the control of cell fate. Thus, these compounds can modulate proliferation, differentiation, and survival in different manners depending on the cell type and its physiopathologic context. However, little is known about the effect of cannabinoids on the cell cycle, the main process controlling cell fate. Here, we show that Delta(9)-tetrahydrocannabinol (THC), through activation of CB2 cannabinoid receptors, reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis. In particular, THC arrests cells in G(2)-M via down-regulation of Cdc2, as suggested by the decreased sensitivity to THC acquired by Cdc2-overexpressing cells. Of interest, the proliferation pattern of normal human mammary epithelial cells was much less affected by THC. We also analyzed by real-time quantitative PCR the expression of CB1 and CB2 cannabinoid receptors in a series of human breast tumor and nontumor samples. We found a correlation between CB2 expression and histologic grade of the tumors. There was also an association between CB2 expression and other markers of prognostic and predictive value, such as estrogen receptor, progesterone receptor, and ERBB2/HER-2 oncogene. Importantly, no significant CB2 expression was detected in nontumor breast tissue. Taken together, these data might set the bases for a cannabinoid therapy for the management of breast cancer.